There are numerous systems that have been designed to deliver active agents to a moist environment such as the oral cavity. Such systems are particularly desirable in comparison to tablets, capsules and other dosage forms that must be swallowed, especially when the patient population includes children, the elderly, or other patients that may have difficulty swallowing.
As described in U.S. Pat. No. 6,750,921 to Kim et al., film-forming agents have been used to manufacture drug delivery formulations for percutaneous or transdermal application, but these necessarily involve an adhesive composition to retain the agent in situ long enough to effect sustained release of the active ingredient.
U.S. Pat. No. 6,264,891 to Zhang et al. describes systems that can be formulated as oral transmucosal patches, lozenges or troches, lollipops or chewing gum. However, these systems can have a relatively long life in the mouth, which may not always be desirable or practical.
Bioerodible films are described in Tapolsky et al., U.S. Pat. No. 5,800,832. The films have an adhesive layer and a non-adhesive backing layer and are intended to adhere to the mucosal surface. Biegajski et al., U.S. Pat. No. 5,700,478, describes a water-soluble pressure-sensitive mucoadhesive suitable for use in a mucosal-lined body cavity.
More recently, rapidly dissolving films have been developed. These include the instant wettability mucoadhesive film intended to adhere to the oral mucosa described in U.S. Pat. Nos. 5,948,430 and 6,709,671 to Zerbe et al. U.S. Pat. No. 6,596,298 to Leung et al. describes fast dissolving orally consumable films that are made of a film-forming polymer, preferably pullulan, to deliver antimicrobial agents and other active agents. These films are nontacky when dry but become tacky upon application to mucosal tissue. Mucoadhesion may not always be desired, however, because the difficulty of properly applying the film decreases patient compliance.
U.S. Patent Publication No. U.S. 2002/0131990 A1, on the other hand, describes a pullulan-free edible film, and indicates that pullulan is costly and not readily available.
A method has recently been developed for tailoring the adhesive properties of polymer compositions useful in a number of applications, including pharmaceutical and cosmetic products. The method is based on new insights into the molecular mechanisms underlying adhesive properties. See, for example, Feldstein et al. (1999) Polym. Mater. Sci. Eng., 81:465-466; Feldstein et al., General approach to the molecular design of hydrophilic pressure-sensitive adhesives, Proceed. 25th Annual Meeting Adhesion Soc. and 2nd World Congress on Adhesion and Relative Phenomena, February 2002, Orlando, Fla., vol. 1 (Oral Presentations), p. 292-294; and Chalykh et al. (2002) J. Adhesion 78(8):667-694. As discussed in the foregoing references, pressure-sensitive adhesion results from the coupling of two apparently incompatible types of molecular structures, and there is a fine balance between strong cohesive interaction energy and enhanced “free volume.”
That is, enhanced free volume in the molecular structure of a PSA (pressure-sensitive adhesive) polymer composition correlates with high tack exhibited at the macroscopic level and a liquid-like fluidity of the PSA material, which, in turn, allow for rapid formation of an adhesive bond. The “cohesive interaction energy” or “cohesion energy” defines the cohesive toughness of the PSA composition and provides the dissipation of detachment energy in the course of adhesive joint failure. Based on these findings, a general method for obtaining novel hydrophilic adhesives was developed and is described in U.S. Pat. No. 6,576,712 to Feldstein et al. In one embodiment, that method involves physically mixing a non-adhesive, hydrophilic, high molecular weight polymer with a relatively low molecular weight plasticizer capable of crosslinking the polymer via hydrogen bonding.
In spite of the development of the art, there remains a need for rapidly dissolving films that have significant drug loading capability, provide ease of handling, dissolve rapidly in the mouth or other moist body location, release drug instantly, and can provide sustained and controlled release of a variety of active agents.